Cutibacterium acnes-macrophage fusion membrane coating Cu/Zn-MOF for psoriasis treatment via pathological innate lymphoid cells inhibition

Psoriasis is a chronic immune-mediated disorder characterized by immune dysregulation and abnormal keratinocyte proliferation. Dysbiosis of the skin microbiota is a key contributor to its pathogenesis, and the expansion of pathogenic type III innate lymphoid cells (ILC3s) plays a central role in disease progression. <i>Cutibacterium acnes</i> (<i>C. acnes</i>) has shown therapeutic potential in alleviating psoriatic symptoms. Here, we engineered a fusion membrane by combining the bacterial cell wall of <i>C. acnes</i> with M2-type macrophage (M2) membranes, and encapsulated Cu/Zn-based metal-organic frameworks (Cu/Zn-MOFs) with antimicrobial and antioxidant properties to form the nanoparticle CM@MOF. In an imiquimod (IMQ)-induced mouse model of psoriasis, CM@MOF significantly reduced <i>Staphylococcus aureus</i> colonization, restored microbial homeostasis, enhanced skin barrier integrity, and suppressed oxidative stress and proinflammatory cytokine expression. Furthermore, CM@MOF effectively reduced the accumulation of pathogenic ILC3s in psoriatic lesions and reestablished local ILC homeostasis. These findings highlight CM@MOF as a promising therapeutic strategy for the treatment of psoriasis.